• 1
    Stellbrink H-J. Clinical and survival benefit of saquinavir (SQV) in combination with zalcitabine (DDC) and zidovudine (ZDV) in untreated minimally treated HIV-infected patients. Abstracts from the Sixth European Conference on Clinical Aspects and Treatment of HIV-Infection, Hamburg, Germany, 1997; (abstract 212): 21.
  • 2
    Haubrich R, Lalezari J, Follansbee SE, et al. Improved survival and reduced clinical progression in HIV-infected patients with advanced disease treated with saquinavir plus zalcitabine. Antiviral Ther 1998; 3: 3342.
  • 3
    Cohen Stuart JWT, Schuurman R, Burger DM, et al. Randomized trial comparing saquinavir soft gelatin capsules versus indinavir as part of triple therapy (CHEESE study). AIDS 1999; 13: F53F58.
  • 4
    Mitsuyasu RT, Skolnik PR, Cohen SR, et al. Activity of the soft gelatin formulation of saquinavir in combination therapy in antiretroviral-naive patients. AIDS 1998; 12: F103F109.
  • 5
    Kohl NE, Emini EA, Schleif WA, et al. Active human immunodeficiency virus protease is required for viral infectivity. Proc Natl Acad Sci USA 1988; 85: 46864690.
  • 6
    Peng C, Bao K, Chang TW, Chang NT. Role of human immunodeficiency virus type 1-specific protease in core protein maturation and viral infectivity. J Virol 1989; 63: 25502556.
  • 7
    Lalezari J. Selecting the optimum dose for a new soft gelatin capsule formulation of saquinavir. J Acquir Immune Defic Syndr Hum Retrovirol 1998; 19: 195196.
  • 8
    Gieschke R, Fotteler B, Buss N, Steimer J-L. Relationships between exposure to saquinavir monotherapy and antiviral response in HIV-positive patients. Clin Pharmacokin 1999; 37: 7586.
  • 9
    Schapiro JM, Winters MA, Stewart F, et al. The effect of high-dose saquinavir on viral load and CD4+ T-cell counts in HIV-infected patients. Ann Intern Med 1996; 124: 10391050.
  • 10
    Gill MJ. Safety profile of soft gelatin formulation of saquinavir in combination with nucleosides in a broad patient population. AIDS 1998; 12: 14001402.
  • 11
    Eagling VA, Back DJ, Barry MG. Differential inhibition of cytochrome P450 isoforms by the protease inhibitors, ritonavir, saquinavir and indinavir. Br J Clin Pharmacol 1997; 44: 190194.
  • 12
    Kempf DJ, Marsh KC, Kumar G, et al. Pharmacokinetic enhancement of inhibitors of the human immunodeficiency virus protease by coadministration with ritonavir. Antimicrob Agents Chemother 1997; 41: 654660.
  • 13
    Carpenter CCJ, Fischl MA, Hammer SM, et al. Antiretroviral therapy for HIV infection in 1997: updated recommendations of the International AIDS Society – USA Panel. JAMA 1997; 277: 19621969.
  • 14
    Cameron DW, Japour AJ, Xu Y, et al. Ritonavir and saquinavir combination therapy for the treatment of HIV infection. AIDS 1999; 13: 213224.
  • 15
    Lal R, Hsu A, Chen P, et al. Single dose pharmacokinetics of ABT-378 in combination with ritonavir. Abstracts of the 37th Interscience Conference on Antimicrobial Agents and Chemotherapy, Toronto, Canada, 1997; (abstract I-194): 279.
  • 16
    Lal R, Hsu A, Granneman GR, et al. Multiple dose safety, tolerability and pharmacokinetics of ABT-378 in combination with ritonavir. Abstracts 5th Conference on Retroviruses and Opportunistic Infections, Chicago, USA, 1998; (Abstract 647): 201.
  • 17
    Tebas P, Patick AK, Kane EM, et al. Virologic responses to ritonavir-saquinavir-containing regimen in patients who had previously failed nelfinavir. AIDS 1999; 13: F23F28.
  • 18
    Cameron DW, Xu Y, Roce R, et al. Three-year follow-up and conditional outcomes survival analysis of ritonavir (RTV) plus saquinavir (SQV) therapy in HIV infection. 7th Conference on Retroviruses and Opportunistic Infections, San Francisco, USA, 2000; (abstract 533).
  • 19
    Hsu A, Granneman GR, Bertz RJ. Ritonavir: clinical pharmacokinetics and interactions with other anti-HIV agents. Clin Pharmacokin 1998; 35: 275291.
  • 20
    Hsu A, Granneman GR, Cao G, et al. Pharmacokinetic interactions between two human immunodeficiency virus protease inhibitors, ritonavir and saquinavir. Clin Pharmacol Ther 1998; 63 (4): 453464.
  • 21
    Merry C, Barry MG, Mulcahy F, et al. Saquinavir pharmacokinetics alone and in combination with ritonavir in HIV-infected patients. AIDS 1997; 11: F29F33.
  • 22
    Profit L, Eagling VA, Back DJ. Modulation of P-glycoprotein function in human lymphocytes and Caco-2 cell monolayers by HIV-1 protease inhibitors. AIDS 1999; 13: 16231627.
  • 23
    Washington CB, Duran GE, Sikic BI, Blaschke TF. Saquinavir is a high affinity substrate for the multidrug transporter, P-glycoprotein. Clin Pharmacol Ther 1997; 61: 193.
  • 24
    Wacher VJ, Wu C-Y, Benet LZ. Overlapping substrate specificities and tissue distribution of cytochrome P4503A and P–glycoprotein: implications for drug delivery and activity in cancer chemotherapy. Mol Carcinog 1995; 13: 129134.
  • 25
    Gatti G, Di Biagio AD, Casazza R, et al. The relationship between ritonavir plasma levels and side-effects: implications for therapeutic drug monitoring. AIDS 1999; 13: 20832089.
  • 26
    Abbott Laboratories. Norvir (ritonavir capsules) soft gelatin (ritonavir oral solution). Prescribing Information, June, 1999.
  • 27
    Pikety C, Race E, Castiel P, et al. Efficacy of a five-drug combination including ritonavir, saquinavir and efavirenz in patients who failed on a conventional triple-drug regimen: phenotypic resistance to protease inhibitors predicts outcome of therapy. AIDS 1999; 13: F71F77.
  • 28
    Saag MS, Kilby M, Ehrensing E, Buss N, Oo CY. Modulation of saquinavir steady-state pharmacokinetics with ‘baby’ doses of ritonavir in healthy volunteers. 7th European Conference on Clinical Aspects and Treatment of HIV-infection, Lisbon, Portugal, 1999; (Abstract 829): 210.
  • 29
    Van Heeswijk RPG, Veldkamp AI, Mulder JW, et al. The steady-state pharmacokinetics of saquinavir in a once daily dosing regimen with a low dose of ritonavir. 7th European Conference on Clinical Aspects and Treatment of HIV-infection, Lisbon, Portugal, 1999; (Abstract 830): 211.
  • 30
    Kurowski M, Müller M, Donath F, Mrozikiewicz M, Möcklinghoff C. Single daily doses of saquinavir achieve HIV-inhibitory concentrations when combined with ‘baby-dose’ ritonavir. Eur J Med Res 1999; 4: 101104.
  • 31
    Gibaldi M & Perrier D. Pharmacokinetics, 2nd edn. New York; Marcel Dekker, 1982.
  • 32
    Hsu A, Granneman GR, Sun E, et al. Assessment of single- and multiple-dose interactions between ritonavir and saquinavir. Abstracts from XI International Conference on AIDS, Vancouver, Canada, 1996.
  • 33
    Watkins PB, Wrighton SA, Schuetz EG, Molowa DT, Guzelian PS. Identification of glucocorticoid-inducible cytochromes P-450 in the intestinal mucosa of rats and man. J Clin Invest 1987; 80: 10291036.
  • 34
    Kolars JC, Lown KS, Schmiedlin-Ren P, et al. CYP3A gene expression in human gut epithelium. Pharmacogenetics 1994; 4: 247259.